Tuberculosis is the leading cause of death in the world from a single infectious agent. In the United States, the incidence of tuberculosis is rising, in large part as a consequence of the AIDS epidemic. Moreover, the emergence of multidrug-resistant tuberculosis looms as a major threat to the public health. A safe and effective vaccine against tuberculosis is sorely needed. The ultimate goal of this proposal is to speed the development of such a vaccine. Previous studies in this laboratory using the guinea pig model of tuberculosis have demonstrated that extracellular proteins of M. tuberculosis induce strong cell-mediated immune responses and a substantial level of protective immunity in this highly susceptible animal model. These studies have demonstrated the feasibility of a subunit vaccine against M. tuberculosis. The purpose of this proposal is to lay the foundation for the next logical stage of development of a subunit vaccine - testing in a primate model. The proposed project will take advantage of a special opportunity that exists for us in The Philippines that will allow these studies to be carried out on high quality cynomolgus monkeys with experienced technical personnel in a newly-constructed dedicated primate facility at a small fraction of their typically enormous cost.